Phase I trials in patients with colon and breast cancer using the anti-LeY solid tumors with immunotoxin LMB-9 are being carried out in collaboration with Dr. Robert Kreitman at NCI and Dr. Peter Hafkemeyer in Freiburg, Germany. LMB-9 is a stable recombinant immunotoxin produced by genetic engineering. Dr. Robert Kreitman has completed a Phase I trial on leukemias and lymphomas with immunotoxin LMB-2 [anti-Tac(Fv)-PE38] that targets the alpha subunit of the IL2 receptor. In this trial, one complete response and many partial responses were observed. Phase II trials are planned in CTCL and CLL. A Phase I trial with immunotoxin (BL22) that targets CD22 present on B-cell malignancies has been completed. Many complete responses in drug resistant Hairy Cell Leukemia were observed. We are planning further trials to determine the safest dose schedule for treatment of HCL, CLL, lymphoma and ALL in children. Immunotoxin SS1P targets the mesothelium antigen present in ovarian cancer, mesothelioma and pancreatic cancer. Phase I trials in which SS1P is given by bolus or continuous infusion are now underway. TGFa-PE38 targets cells expressing high levels of EGF receptor. A Phase I trial is being carried out at Duke in which TGFa-PE38 is infused into the tumors of patients with recurrent glioblastomas.